Recent anatomical and physiological data support the notion that, in vertebrates, neural processing within the olfactory bulb is regulated by both excitatory and inhibitory centrifugal influences. The functional role of centrifugal inputs depends upon their postsynaptic targets in the olfactory bulb. However, detailed assessment of synaptic circuits of identified excitatory and inhibitory centrifugal afferent has not been made. In Experiment 1, the excitatory (cholinergic) and inhibitory (GABAergic) inputs to the rat olfactory bulb from the horizontal limb of the diagonal band nucleus will be examined. The localization of identified bulbopetal axon terminals with different neurotransmitter specificities and their postsynaptic intrabulbar targets will be established using anterograde axonal tracing techniques and electron microscopic immunocytochemistry. Synaptic organization of afferent inputs tot he olfactory bulb from the nucleus of the horizontal limb of the diagonal band is of particular interest because of the involvement of this area in neurodegenerative processes. For example, in Alzheimer's disease which is often accompanied by early olfactory dysfunction. In Experiment 2, morphological and neurotransmitter bases for central regulation of the olfactory bulb will be studied in the tiger salamander. Despite the fact that the salamander is becoming a standard model for investigations of olfaction, surprisingly little information is available about the centrifugal innervation of the olfactory bulb in this species. The localization of bulbopetal neurons, especially cholinergic and GABAergic cells, and their synaptic connections with intrinsic bulbar neurons will be examined using axonal tracing and immunocytochemical techniques. These two Experiments will lead to a better understanding of neural circuits involved in the central regulation of intrabulbar olfactory processing in the rat and will give the first structural and neurochemical descriptions of the centrifugal olfactory system in the salamander. These studies represent a primary component of the Center's basic research activities and provide information of potential value to other Center projects. For example, the sensory aberrations observed in some of the neurodegenerative disorders, studied in Project 1, may be due, at least in part, to changes in centrifugal olfactory pathways. This may also be true of the changes in function observed following pharmacologic manipulations of the cholinergic system in Project 4.